The long-term objective of the proposed research is to understand, at the cellular and network levels, mechanisms regulating synaptic transmission in the vertebrate central nervous systme. The goldfish Mauthner (M-) cell and its defined inputs will be used as the experimental model; the identified synapeses in this system serve as valuable material for analyses not readily accomplished in mammalian preparations. Specific objectives include a physiological analysis of the properties of transmitter release by eighth nerve afferents onto the M-cell's lateral dendrite. These fibers establish morphologically mixed synapses on the M-cell and their terminals contain multiple active zones. Simultaneous intracellular recordings, dye injections, and quantal analysis will be used to determine if single active zones function as quantal units. Quantal analysis of tacilitation will also be conducted. Finally, ineffective synapses established by these endings and by inhibitory inputs to the M-cell will be studied electrophysiologically and morphologically, in order to see if they establish structurally normal synapses and if they can be transformed into transmitting junctions. Two possible postsynaptic mechanisms of synaptic plasticity will also be investigated with voltage clamp techniques: 1) the concept that adjacent presynaptic endings have overlapping postsynaptic domains, and 2) voltage dependent changes in inhibitory conductances. Mechanisms regulating synaptic transmission and its plasticity are critical to numerous health-related issues, such as learning and memory, developmental and environmental modifications of nervous system function, and drug or transmitter-related dysfunctions. Analysis of synapse organizaiton at the single cell level will provide information basic to our understanding of nervous system function in such normal and pathological conditions.